N,n - dimethyl - n - (ch(ch3)-c8-c16 alkyl) - n-3 - nitro - 4 - methoxybenzylammonium chlorides



United States Patent Ofice Patented Oct. 6, 1970 ABSTRACT OF THE DISCLOSURE N,N dimethyl N [CH(CH )C -C alkyl]-N-3- nitro 4 methoxybenzyl ammonium chlorides exhibit high germicidal, algicidal and fungicidal activity in hard water.

This invention relates to germicidal, fungicidal and algicidal quaternary ammonium compounds and to methods for their preparation. Quaternary ammonium compounds have enjoyed wide use as antiseptic agents. However, one of the major problems'in the quaternary ammonium germicide art has been to find quaternary ammonium compounds which are highly effective, but which are cheap. It is particularly desired to have a cheap quaternary ammonium composition which exhibits high germicidal, algicidal and fungicidal activity in hard water.

It is accordingly a principal object of this invention to provide cheap quaternary ammonium compositions having a high antimicrobial activity and useful as sanitizing agents, algicides, fungicides and deodorants and for other utilities well known in the quaternary art.

It is a further object of this invention to provide compositions that comply with the standards of the United States Public Health Service and of industry in certain sanitation applications such as sanitizing food utensils, disinfecting swimming pools and the like.

A still further object is to provide improved methods for controlling bacteria, fungi and algae in aqueous systems by means of the addition of improved quaternary ammonium compositions.

All of these objects have been attained by the instant invention.

In one of its composition aspects, the present invention is described as residing in the concept of an N,N-di (lower alkyl) N [CH(CH )R] N-(R)-ammonium chloride wherein R is alkyl of from 6 to 18 carbon atoms and R is a member of the group Consisting of lower alkyl, lower alkenyl, and benzyl.

As used herein, the term alkyl means a monovalent straightor branched-chain saturated aliphatic hydrocarbon radical. The alkyl radicals envisioned for the purpose of this invention include for example the branched and unbranched radicals hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pendtadecyl, hexadecyl, heptadecyl, octadecyl, and the like.

As used herein, lower alkyl radicals are alkyl radicals as above having from 1 to 6 carbon atoms.

As used herein, the term lower alkenyl means straightor branched-chain aliphatic hydrocarbon radicals having at least one carbon-to-carbon double bond and having from 2 to 6 carbon atoms.

As used herein, the term benzyl means the monovalent radical obtained when a hydrogen atom attached to the methyl group of toluene is removed. As will be obvious to one skilled in this art, the substitution of simple moieties on the benzene ring of the benzyl radical such as lower alkyl, halo (i.e., chloro, bromo, iodo, and fiuoro) lower alkoxy, lower alkylmercapto, nitro, and -trifluoro methyl, does not adversely affect the germicidal, algicidal, and fungicidal activities of the compositions bearing the benzyl radical on the quaternary nitrogen atom, and such substituted compounds are the full equivalents of the compositions herein claimed.

In another of its composition aspects, the present invention is described as residing in the concept of a composition comprising a mixture of N,N-di(lower alkyl)- N CH(CH )R"] N-(=R')-ammonium chlorides, wherein R is alkyl of from 6 to 18 carbon atoms having an average of 10.5-11.5 carbon atoms and R is a member of the group consisting of lower alkyl, lower alkenyl and benzyl.

An important avdantage offered by the compositions of this invention resides in their economy. Not only are the compositions readily prepared from cheap, commercially abundant starting materials, but in addition they are particularly effective as germicides, algicides, and fungicides.

The novel compounds of this invention can be prepared by the following process:

An alpha-olefin is catalytically hydrochlorinated by adding hydrogen chloride to the double bond in the absence of actinic light or peroxides. The resulting 2-chloroalkane is caused to react with a di-(lower alkyl) amine to give 2 [di (lower alkyl) amino]alkane, which, when caused to react with a quaternizing agent, RCl (or R"Cl), gives the desired product.

In practice, the hydrochlorina-tion step has been found to proceed readily at reduced temperatures (O-'10 C.) in the presence of a Lewis acid. We generally prefer to use stannic chloride, 'but other Lewis acids, for example, aluminum chloride, ferric chloride, zinc chloride and the like are satisfactory.

The reaction of the 2-chlor0alkanes with a di-(lower alkyl)amine is conveniently carried out in aqueous solution, at a pressure of 500 1000 pounds per square inch and a temperature of about ZOO-250 C. The use of an excess of the amine reduces the formation of unwanted quaternaries at this stage of the process.

Quaternization of the 2 di (lower alkyl)aminoalkane with the quaternizing agent, R'Cl (or R'Cl), is readily accomplished in aqueous solution at about 60- C. A slight excess of quaternizing agent is desirable for high yields at this step; the excess is hydrolyzed and removed in the purification of the quaternary.

While the product of this invention can be isolated in the form of a mixture of the pure quaternary salts, We prefer to prepare the compositions in the form of their solutions (aqueous or aqueous-alcoholics) containing approximately 50 percent quaternary. In this form the quaternary mixture is conveniently packaged, shipped and used.

The phenol coeflicients of exemplary compositions of this invention are given in Table I, as follows:

TABLE I.PHENOL COEFFICIENTS OF N,N-DIME'IHYLN- BENZYIrZ-ALKYLAMMONIUM GHLO RIDES, ALKYL=Cu-C15 [Phenol coefficient at 20 0.]

alkylammonium chloride.

The anion of the quaternary ammonium salts of this invention is disclosed throughout as chloride, because the chloride salts are the cheapest to product. It will be understood by one skilled in the art that all anions known in the quaternary germicide art are equivalent insofar as their germicidal activity is concerned.

The following examples serve to further illustrate the invention, but the latter is limited thereto:

EXAMPLE 1 (A) 2-chl0roalkanes Three moles of alpha-olefin (RCHCH wherein R is alkyl of from 9 to 13 carbon atoms) having an average molecular weight of approximately 180, and having the following approximate analysis:

Olefin: Percent 1 C 14 C 23 C 23 C14 24 C 14 C 1 were caused to react in the absence of a solvent with hydrogen chloride at 1-5" C. in the presence of 5 percent of stannic chloride as a catalyst. The reaction was complete in about eight hours. The catalyst was removed by extraction with dilute hydrochloric acid, water, and dilute sodium bicarbonate solution, and the product was dried over anhydrous magensium sulfate. The resulting 2-chloroalkanes were obtained in a yield of 97.5 percent as a crude mixture, n =l.443 8, which assayed at 100 percent chloroalkane.

(B) Z-dimethylaminoalkane An autoclave was charged with a mixture containing 1 mole of crude 2-chloroalkane (above), 1 mole of sodium hydroxide as a 50 percent aqueous solution, and 1.5 moles of dimethylamine as a percent aqueous solution. The autoclave temperature was raised to 240 C. over a period of three hours and was maintained at 240 C. i2 C. for 24 hours. The autoclave pressure was 760 p.s.i. (pounds per square inch). After coling, the reaction mixture was separated, washed with saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The Z-dimethylaminalkane mixture was then distilled. A crude yield of 91.4 percent of theory was obtained.

(-C) N,N-dimethyl-N-benzyl-2-alkylammonium chloride A reaction vessel was charged with 216.0 g. of 2-dimethylaminoalkane (Example 1B) and 47.5 ml. of water,

and the mixture was heated to 80 C. During a period of 5.5 hours 105.0 g. of benzyl chloride was added while maintaining a reaction temperature of 8085 C. Stirring was continued at 80-85 C. for one hour, and the mixture was boiled until the pH was about 7.6. An additional 5.0 g. of benzyl chloride and 25 ml. of water was added in increments with alternate stirring and boiling until the pH of the mixture was 6.8. Ten ml. of 15 percent sodium carbonate solution and heating at 80-85 C. were then required to neutralize the slight excess of benzyl chloride and bring the pH to 8.0. The mixture was then steam distilled for 2.5 hours to remove contaminants. The purified quaternary solution was diluted with 45.0 ml. of distilled water, treated with activated charcoal, and filtered. After washing the filter cake and further dilution of the product with distilled water, there was obtained 522.0 g. of a 53.50 percent solution of N,N-dimethyl-N- benzyl-Z-alkylammonium chloride, representing a process yield of 82.7 percent. The phenol 'coelficients of the product are given in Table I.

4 EXAMPLE 2 N-benzyl-N,N-dimethyl-Z-alkylammonium chloride Following the procedure given in Examples 1A, 1B and 1C, a mixture of N,N-dimethyl-N-benzyl-2-alkylammonium chloride was prepared from alpha-olefins having a chain length of C C The average molecular weight of the product was 414.7 and the solution assayed at 50.21% quarternary.

Biological testing according to standard testing procedures revealed the following phenol coefiicients for this product:

Organism: Phenol coeff. at 20 C. Staph aureus 357 Sal. typhosa 388 EXAMPLE 3 N-benzyl-N,N-dimethyl-Z-alkylammonium chloride Following the procedure given in Examples 1A, 1B and 1C, a mixture of N-benzyl-N,N-dimethyl-Z-alkylammonium chloride was prepared from a mixture of alphaolefins having a chain length of C C The average molecular weight of the product was 383.2, and the solution assayed at 49.97 percent quaternary.

Biological testing according to standard testing procedures revealed the following phenol coeflicients for this product:

Organism: Phenol coeff. at 20 C. Staph aureus 428 Sal. typhosa 388 EXAMPLE 4 N-allyl-N,N-dimethyl-Z-alkylammonium chloride Following the procedure given in Example 1C, N-allyl- N,N-dimethyl-2-alkylammonium chloride having an alkyl chain length of C C was prepared from allyl chloride and the Z-dimethylaminoalkane described in Example 1B. The average molecular weight of this product was 301.6 and the solution assayed at 50.07 percent quaternary.

Biological testing according to standard testing procedures revealed the following phenol coetficients for this product:

Organism: Phenol coeff. at 20 C. Staph aureus 440 Sal. typhosa 278 EXAMPLE 5 N-(4-chlorobenxyl--N,N-dimethy1-2-alkylammonium chloride Following the procedure given in Example 1C, N-(4- chlorobenzyl)-N,N-dimethyl-Z-alkylammonium chloride having an alkyl chain length of C C was prepared from p-chlorobenzyl chloride and the 2-dimethylaminoalkane described in Example 1B. The average molecular weight of this product, having the structural formula was 386.1, and the solution assayed at 53.8 percent quaternary.

The phenol coefficients for this product are given in Table I.

EXAMPLE 6 j N -dichlorobenzyl-N,Ndimethyl-2-alkylammonium chloride Following the procedure given in Example 10, N-dichlorobenzyl N,N dimethyl-Z-alkylammom'um chloride having an alkyl chain length of C -C was prepared from mixed dichlorobenzyl chlorides and the Z-dimethyl aminoalkane described in Example 1B. The product, having the structural formula 118 or a; e R"CHNCHr-@ 01 had an average molecular weight of 420.6, and the solution assayed at 52.3 percent quaternary.

The phenol coefficients for this product are given in Table 1.

EXAMPLE 7 N,N-dimethyl-N-ethylbenzyl-Z-alkylammonium chloride Following the procedure given in Example 1C, N,N- dimethyl N ethylbenzyl-2-alkylammonium chloride having an alkyl chain length of C -C was prepared from mixed ethylbenzyl chlorides containing about 70 percent p-ethyl-benzyl chloride and about 30 percent o-ethylbenzyl chloride and the Z-dimethylaminoalkane described in Example .113. The product having the structural formula CzHs Q 6 I Q 1 CH: Ha

had an average molecular weight of 379.8, and the solution assayed at 52.94 percent quaternary.

average molecular weight of this product, having the structural formula N02 ea (3H3 R"CH-NCH;r--OCH3 o1 Ha Hs was 426.7, and the solution assayed at 50.33 percent quaternary.

Biological testing according to standard testing procedures revealed the following phenol coeificients for this product:

Organism: Phenol coeflicient at 20 C. Staph aureus 785 Sal. typhosa 722 Moreover, this product was highly effective as a germicidal agent in very hard water, as determined by the Chambers test method.

EXAMPLE 9 (A) 2-diethylarninoalkane Following the procedure given in Example 1B, the 2-chloroalkane mixture prepared as in Example 1A is caused to react with aqueous diethylamine to give a mixture of Z-diethylaminoalkane having an alkyl chain length Of C C (B) N-benzy1-N,N-diethyl-Z-alkylammonium chloride Following the procedure given in Example 10, the 2- diethylaminoalkane prepared in Example 9A is quaternized with benzyl chloride to produce N-benZyl-N,N- diethyl-Z-alkylammonium chloride having an alkyl chain length of C -C As further illustrations of our invention, the following compositions can also be prepared from Z-dimethylaminoalkane and the indicated quaternizing agent according to the procedure given in Example 1C:

alkylammonium chloride.

4,5-diehloro-2-methylb enzyl chloride. N(4,5-dichloro-2-methylb enzyl) -N,N-dimethyl- 2-a1kylammonium chloride.

Biological testing by standard testing procedures revealed the following phenol coeflicients for this product:

Organism: Phenol coefficient at 20C. Staph aureus 428 Sal. typhosa 333 EXAMPLE 8 N,N-dimethyl-N- (4-methoxy-3 -nitrobenzyl -2-alkylammonium chloride Following the procedure given in Example 1C, N,N- dimethyl-N-(4-methoxy 3 nitrobenzyl)-2-alky1ammonium chloride having an alkyl chain length of C -C was prepared from 4-methoxy-3-nitrobenzyl chloride and the As will be evident to the skilled chemist, the mixtures of alpha-olefins, 2-chloro-alkanes and 2-di(loWer alkyl)- aminoalkanes can be separated from one another by physical means, for example, fractional distillation or preferably vapor-phase chromatographic separation, to give the individual alpha-olefins, 2-chloroalkanes, or Z-di- (lower alkyl) aminoalkane in essentially pure form. From these intermediates, the individual quaternary ammonium compounds can be prepared in essentially pure form by the methods disclosed herein.

We claim:

1. N,N-dimethyl N [CH(CH )R]-N-benzyl-am- Z-dimethylaminoalkane described in Example 1B. The monium chloride wherein R is alkyl of from 9- to 13 car- 7 8 bon atoms and benzyl is substituted in the 3-position by 2,432,905 12/1947 Kharasch et a1. 260-326 nitro and in the 4-position by methoxy. 3,287,410 11/ 1966 Dudzinski et a1 260583 2. A mixture of 3,287,411 11/1966 Wakeman et a1. 260-583 XR N,N-di-(1ower alkyl)-N-[CH(CH )R]-N-(R) OTHER REFERENCES Hucker et al.: Chemical Abstracts, vol. 41, pp. ammonium chlorides wherein R" is alkyl of from 6 to 7667-8 (1947). 18 carbon atoms and having an average of ,10.511.5 Morin: Chemical Abstracts, Vol. 47, pp. 1850-1 carbon atoms, and R" is benzyl substituted in the 3-posi- (1953) tion by nitro and in the 4-position by methoxy.

FLOYD D. HIGEL, Primary Examiner References Cited UNITED STATES PATENTS 2,191,922 2/1940 Br'uson 260567.6 261F583, 663;424329 Invcntorfif) Crounse, Bonta-ic Floss appears in the above-identifitd patent It is certified that error corrected as shown below:

and that said Letters Eatcnt are hereby Column 1,- line 60, "pendtadeoyl" should read '-.--pentadeoy1-. Column 5, line 15; (R-CHCH should read --'(R-cH=cH line 48, "2dimethylamina1kane should read --2-dimethylam1noalkane-- Column 4, l1ne 52' "N- (4-chlorobenxy'l should read N-(Q-Chlorobenzyl Signed and sealed this 15th day of Au ust 1972.

(SEAL) Attest: Y

EDWARD I E.FLETCHER,-JR. I .ROBERT GOTTSCHALK Attes'ting Officer Commissioner of Patents 

